Multicenter Registry of Adenomas of the Pituitary and Related Disorders: Initial Description of Cushing Disease Cohort, Surgical Outcomes, and Surgeon Characteristics.

BACKGROUND AND OBJECTIVES: To address the lack of a multicenter pituitary surgery research consortium in the United States, we established the Registry of Adenomas of the Pituitary and Related Disorders (RAPID). The goals of RAPID are to examine surgical outcomes, improve patient care, disseminate best practices, and facilitate multicenter surgery research at scale. Our initial focus is Cushing disease (CD). This study aims to describe the current RAPID patient cohort, explore surgical outcomes, and lay the foundation for future studies addressing the limitations of previous studies. METHODS: Prospectively and retrospectively obtained data from participating sites were aggregated using a cloud-based registry and analyzed retrospectively. Standard preoperative variables and outcome measures included length of stay, unplanned readmission, and remission. RESULTS: By July 2023, 528 patients with CD had been treated by 26 neurosurgeons with varying levels of experience at 9 academic pituitary centers. No surgeon treated more than 81 of 528 (15.3%) patients. The mean ± SD patient age was 43.8 ± 13.9 years, and most patients were female (82.2%, 433/527). The mean tumor diameter was 0.8 ± 2.7 cm. Most patients (76.6%, 354/462) had no prior treatment. The most common pathology was corticotroph tumor (76.8%, 381/496). The mean length of stay was 3.8 ± 2.5 days. The most common discharge destination was home (97.2%, 513/528). Two patients (0.4%, 2/528) died perioperatively. A total of 57 patients (11.0%, 57/519) required an unplanned hospital readmission within 90 days of surgery. The median actuarial disease-free survival after index surgery was 8.5 years. CONCLUSION: This study examined an evolving multicenter collaboration on patient outcomes after surgery for CD. Our results provide novel insights on surgical outcomes not possible in prior single-center studies or with national administrative data sets. This collaboration will power future studies to better advance the standard of care for patients with CD.

Impact of Frailty on Surgical Outcomes of Patients With Cushing Disease Using the Multicenter Registry of Adenomas of the Pituitary and Related Disorders Registry.

BACKGROUND AND OBJECTIVES: Despite growing interest in how patient frailty affects outcomes (eg, in neuro-oncology), its role after transsphenoidal surgery for Cushing disease (CD) remains unclear. We evaluated the effect of frailty on CD outcomes using the Registry of Adenomas of the Pituitary and Related Disorders (RAPID) data set from a collaboration of US academic pituitary centers. METHODS: Data on consecutive surgically treated patients with CD (2011-2023) were compiled using the 11-factor modified frailty index. Patients were classified as fit (score, 0-1), managing well (score, 2-3), and mildly frail (score, 4-5). Univariable and multivariable analyses were conducted to examine outcomes. RESULTS: Data were analyzed for 318 patients (193 fit, 113 managing well, 12 mildly frail). Compared with fit and managing well patients, mildly frail patients were older (mean ± SD 39.7 ± 14.2 and 48.9 ± 12.2 vs 49.4 ± 8.9 years, P < .001) but did not different by sex, race, and other factors. They had significantly longer hospitalizations (3.7 ± 2.0 and 4.5 ± 3.5 vs 5.3 ± 3.5 days, P = .02), even after multivariable analysis (ß = 1.01, P = .007) adjusted for known predictors of prolonged hospitalization (age, Knosp grade, surgeon experience, American Society of Anesthesiologists grade, complications, frailty). Patients with mild frailty were more commonly discharged to skilled nursing facilities (0.5% [1/192] and 4.5% [5/112] vs 25% [3/12], P < .001). Most patients underwent gross total resection (84.4% [163/193] and 79.6% [90/113] vs 83% [10/12]). No difference in overall complications was observed; however, venous thromboembolism was more common in mildly frail (8%, 1/12) than in fit (0.5%, 1/193) and managing well (2.7%, 3/113) patients (P = .04). No difference was found in 90-day readmission rates. CONCLUSION: These results demonstrate that mild frailty predicts CD surgical outcomes and may inform preoperative risk stratification. Frailty-influenced outcomes other than age and tumor characteristics may be useful for prognostication. Future studies can help identify strategies to reduce disease burden for frail patients with hypercortisolemia.

Resection of Secreting Right Carotid Body Paraganglioma: 2-Dimensional Operative Video.

Secreting carotid body paragangliomas are very rare entities that account for less than 1% of all tumors of the head and neck region.1-3 These vascular lesions splay the internal and external carotid arteries as they enlarge and cause increased catecholamine production in affected individuals. Surgical resection is definitive treatment, but preoperative embolization of the tumor can decrease its vascular supply and aid in surgery. Patients undergoing treatment require preoperative administration of alpha and beta adrenergic blockade to avoid intraoperative and postoperative complications. In this case, a 49-year-old woman presented with a growing neck mass compatible with a carotid body tumor. Preoperative MRI demonstrated a lesion splaying the external and internal carotid arteries. Angiogram demonstrated a vascular tumor, which was embolized before surgery. The patient consented to the procedure and the publication of her case and images. The University of Utah does not require Institutional Review Board approval for the presentation of a single case. This step-by-step video illustrates the surgical resection of her secreting right carotid body paraganglioma. Skull base neurosurgeons must understand the anatomy of vessels and nerves of the neck to safely and successfully resect such tumors.

Predictors of Durable Remission After Successful Surgery for Cushing Disease: Results From the Multicenter RAPID Registry.

BACKGROUND AND OBJECTIVE: Cushing disease (CD) affects mortality and quality of life along with limited long-term remission, underscoring the need to better identify recurrence risk. The identification of surgical or imaging predictors for CD remission after transsphenoidal surgery has yielded some inconsistent results and has been limited by single-center, single-surgeon, or meta-analyses studies. We sought to evaluate the multicenter Registry of Adenomas of the Pituitary and Related Disorders (RAPID) database of academic US pituitary centers to assess whether robust nonhormonal recurrence predictors could be elucidated. METHODS: Patients with treated CD from 2011 to 2023 were included. The perioperative and long-term characteristics of CD patients with and without recurrence were assessed using univariable and multivariable analyses. RESULTS: Of 383 patients with CD from 26 surgeons achieving postoperative remission, 288 (75.2%) maintained remission at last follow-up while 95 (24.8%) showed recurrence (median time to recurrence 9.99 ± 1.34 years). Patients with recurrence required longer postoperative hospital stays (5 ± 3 vs 4 ± 2 days, P = .002), had larger average tumor volumes (1.76 ± 2.53 cm3 vs 0.49 ± 1.17 cm3, P = .0001), and more often previously failed prior treatment (31.1% vs 14.9%, P = .001) mostly being prior surgery. Multivariable hazard prediction models for tumor recurrence found younger age (odds ratio [OR] = 0.95, P = .002) and Knosp grade of 0 (OR = 0.09, reference Knosp grade 4, P = .03) to be protective against recurrence. Comparison of Knosp grade 0 to 2 vs 3 to 4 showed that lower grades had reduced risk of recurrence (OR = 0.27, P = .04). Other factors such as length of stay, surgeon experience, prior tumor treatment, and Knosp grades 1, 2, or 3 failed to reach levels of statistical significance in multivariable analysis. CONCLUSION: This multicenter study centers suggests that the strongest predictors of recurrence include tumor size/invasion and age. This insight can help with patient counseling and prognostication. Long-term follow-up is necessary for patients, and early treatment of small tumors may improve outcomes.

Management of Symptomatic Hemorrhage From a Developmental Venous Anomaly.

Developmental venous anomalies (DVAs) are clinically benign, low-flow vascular malformations that classically hemorrhage only when associated with a cerebral cavernous malformation. It is very rare for an isolated DVA to hemorrhage. Resection of the DVA is generally contraindicated because of the high risk of venous infarct. We present the case of a large symptomatic hemorrhage stemming from an isolated DVA. The hematoma was evacuated and the hemorrhagic portion of the DVA was resected. This case demonstrates that in rare circumstances, careful resection can successfully treat hemorrhagic DVAs.

Examining barriers to care: a retrospective cohort analysis investigating the relationship between hospital volume and outcomes in pediatric patients with cerebral arteriovenous malformations.

OBJECTIVE: Comprehensive data on treatment patterns of pediatric cerebral arteriovenous malformations (AVMs) are lacking. The authors' aim was to examine national trends, assess the effect of hospital volume on outcomes, and identify variables associated with treatment at high-volume centers. METHODS: Pediatric AVM admissions (for ruptured and unruptured lesions) occurring in the US in 2016 and 2019 were identified using the Kids' Inpatient Database. Demographics, treatment methods, costs, and outcomes were recorded. The effect of hospital AVM volume on outcomes and factors associated with treatment at higher-volume hospitals were analyzed. RESULTS: Among 2752 AVM admissions identified, 730 (26.5%) patients underwent craniotomy, endovascular treatment, or a combination. High-volume (vs low-volume) centers saw lower proportions of Black (8.7% vs 12.9%, p < 0.001) and lowest-income quartile (20.7% vs 27.9%, p < 0.001) patients, but were more likely to provide endovascular intervention (19.5%) than low-volume institutions (13.7%) (p = 0.001). Patients treated at high-volume hospitals had insignificantly lower numbers of complications (mean 2.66 vs 4.17, p = 0.105) but significantly lower odds of nonroutine discharge (OR 0.18 [95% CI 0.06-0.53], p = 0.009) and death (OR 0.13 [95% CI 0.02-0.75], p = 0.023). Admissions at high-volume hospitals cost more than at low-volume hospitals, regardless of whether intervention was performed ($64,811 vs $48,677, p = 0.001) or not ($64,137 vs $33,779, p < 0.001). Multivariable analysis demonstrated that Hispanic children, patients who received AVM treatment, and those in higher-income quartiles had higher odds of treatment at high-volume hospitals. CONCLUSIONS: In this largest study of US pediatric cerebral AVM admissions to date, higher hospital volume correlated with several better outcomes, particularly when patients underwent intervention. Multivariable analysis demonstrated that higher income and Hispanic race were associated with treatment at high-volume centers, where endovascular care is more common. The findings highlight the fact that ensuring access to appropriate treatment of patients of all races and socioeconomic classes must be a focus.

Subtemporal Approach for the Treatment of Ruptured and Unruptured Distal Basilar Artery Aneurysms: Is There a Contemporary Use?

BACKGROUND AND OBJECTIVES: Distal basilar artery aneurysms (DBAs) are high-risk lesions for which endovascular treatment is preferred because of their deep location, yet indications for open clipping nonetheless remain. The subtemporal approach allows for early proximal control and direct visualization of critical posterior perforating arteries, especially for posterior-projecting aneurysms. Our objective was to describe our clinical experience with the subtemporal approach for clipping DBAs in the evolving endovascular era. METHODS: This was a retrospective, single-institution case series of patients with DBAs treated with microsurgery over a 21-year period (2002-2023). Demographic, clinical, and surgical data were collected for analysis. RESULTS: Twenty-seven patients underwent clipping of 11 ruptured and 16 unruptured DBAs with a subtemporal approach (24 female; mean age 53 years). Ten patients had expanded craniotomies for treatment of additional aneurysms. The aneurysm occlusion rate was 100%. Good neurological outcomes as defined by the modified Rankin Scale score ≤2 and Glasgow Outcome Scale score ≥4 were achieved in 21/27 patients (78%). Two patients died before hospital discharge, one from vasospasm-induced strokes and another from an intraoperative myocardial infarction. CONCLUSION: These results demonstrate that microsurgical clip ligation of DBAs using the subtemporal approach remains a viable option for complex lesions not amenable to endovascular management.

Frailty as a predictor of poor outcomes in patients with chronic subdural hematoma (cSDH): A systematic review of literature.

Objective: In recent years, frailty has been reported to be an important predictive factor associated with worse outcomes in neurosurgical patients. The purpose of the present systematic review was to analyze the impact of frailty on outcomes of chronic subdural hematoma (cSDH) patients. Methods: We performed a systematic review of literature using the PubMed, Cochrane library, Wiley online library, and Web of Science databases following PRISMA guidelines of studies evaluating the effect of frailty on outcomes of cSDH published until January 31, 2023. Results: A comprehensive literature search of databases yielded a total of 471 studies. Six studies with 4085 patients were included in our final qualitative systematic review. We found that frailty was associated with inferior outcomes (including mortality, complications, recurrence, and discharge disposition) in cSDH patients. Despite varying frailty scales/indices used across studies, negative outcomes occurred more frequently in patients that were frail than those who were not. Conclusions: While the small number of available studies, and heterogenous methodology and reporting parameters precluded us from conducting a pooled analysis, the results of the present systematic review identify frailty as a robust predictor of worse outcomes in cSDH patients. Future studies with a larger sample size and consistent frailty scales/indices are warranted to strengthen the available evidence. The results of this work suggest a strong case for using frailty as a pre-operative risk stratification measure in cSDH patients.

Preservation of cranial nerve function in large and giant trigeminal schwannoma resection: a case series.

BACKGROUND: Trigeminal schwannomas (TSs) are intracranial tumors that can cause significant brainstem compression. TS resection can be challenging because of the risk of new neurologic and cranial nerve deficits, especially with large (≥ 3 cm) or giant (≥ 4 cm) TSs. As prior surgical series include TSs of all sizes, we herein present our clinical experience treating large and giant TSs via microsurgical resection. METHODS: This was a retrospective, single-surgeon case series of adult patients with large or giant TSs treated with microsurgery in 2012-2023. RESULTS: Seven patients underwent microsurgical resection for TSs (1 large, 6 giant; 4 males; mean age 39 ± 14 years). Tumors were classified as type M (middle fossa in the interdural space; 1 case, 14%), type ME (middle fossa with extracranial extension; 3 cases, 43%), type MP (middle and posterior fossae; 2 cases, 29%), or type MPE (middle/posterior fossae and extracranial space; 1 case, 14%). Six patients were treated with a frontotemporal approach (combined with transmastoid craniotomy in the same sitting in one patient and a delayed transmaxillary approach in another), and one patient was treated using an orbitofrontotemporal approach. Gross total resection was achieved in 5 cases (2 near-total resections). Five patients had preoperative facial numbness, and 6 had immediate postoperative facial numbness, including two with worsened or new symptoms. Two patients (28%) demonstrated new non-trigeminal cranial nerve deficits over mean follow-up of 22 months. Overall, 80% of patients with preoperative facial numbness and 83% with facial numbness at any point experienced improvement or resolution during their postoperative course. All patients with preoperative or new postoperative non-trigeminal tumor-related cranial nerve deficits (4/4) experienced improvement or resolution on follow-up. One patient experienced tumor recurrence that has been managed conservatively. CONCLUSIONS: Microsurgical resection of large or giant TSs can be performed with low morbidity and excellent long-term cranial nerve function.

Multicenter Registry of Adenomas of the Pituitary and Related Disorders: Initial Description of Cushing Disease Cohort, Surgical Outcomes, and Surgeon Characteristics.

BACKGROUND AND OBJECTIVES: To address the lack of a multicenter pituitary surgery research consortium in the United States, we established the Registry of Adenomas of the Pituitary and Related Disorders (RAPID). The goals of RAPID are to examine surgical outcomes, improve patient care, disseminate best practices, and facilitate multicenter surgery research at scale. Our initial focus is Cushing disease (CD). This study aims to describe the current RAPID patient cohort, explore surgical outcomes, and lay the foundation for future studies addressing the limitations of previous studies. METHODS: Prospectively and retrospectively obtained data from participating sites were aggregated using a cloud-based registry and analyzed retrospectively. Standard preoperative variables and outcome measures included length of stay, unplanned readmission, and remission. RESULTS: By July 2023, 528 patients with CD had been treated by 26 neurosurgeons with varying levels of experience at 9 academic pituitary centers. No surgeon treated more than 81 of 528 (15.3%) patients. The mean ± SD patient age was 43.8 ± 13.9 years, and most patients were female (82.2%, 433/527). The mean tumor diameter was 0.8 ± 2.7 cm. Most patients (76.6%, 354/462) had no prior treatment. The most common pathology was corticotroph tumor (76.8%, 381/496). The mean length of stay was 3.8 ± 2.5 days. The most common discharge destination was home (97.2%, 513/528). Two patients (0.4%, 2/528) died perioperatively. A total of 57 patients (11.0%, 57/519) required an unplanned hospital readmission within 90 days of surgery. The median actuarial disease-free survival after index surgery was 8.5 years. CONCLUSION: This study examined an evolving multicenter collaboration on patient outcomes after surgery for CD. Our results provide novel insights on surgical outcomes not possible in prior single-center studies or with national administrative data sets. This collaboration will power future studies to better advance the standard of care for patients with CD.

Transmaxillary approach for resection of maxillary division trigeminal schwannoma at foramen rotundum.

BACKGROUND: The foramen rotundum and anterior cavernous sinus have traditionally been accessed by transcranial approaches that are limited by the high density of critical neurovascular structures. The transmaxillary approach provides an entirely extradural route to the foramen rotundum and anterior cavernous sinus. METHOD: This patient with neurofibromatosis and facial pain with trigeminal schwannoma at the foramen rotundum was successfully treated by transmaxillary resection of the tumor. This approach allowed for a direct extradural access to the pathology, with bony decompression and tumor resection, avoiding transcranial routes. CONCLUSION: The transmaxillary approach provides a safe and entirely extradural corridor to access smaller localized skull base lesions at and surrounding the cavernous sinus.

The risk analysis index demonstrates superior discriminative ability in predicting extended length of stay in pituitary adenoma resection patients when compared to the 5-point modified frailty index.

Objective: To compare the predictive abilities of two frailty indices on post-operative morbidity and mortality in patients undergoing pituitary adenoma resection. Methods: The National Surgical Quality Improvement Program (NSQIP) database was used to retrospectively collect data for patients undergoing pituitary adenoma resection between 2015-2019. To compare the predictive abilities of two of the most common frailty indices, the 5-point modified frailty index (mFI-5) and the risk analysis index (RAI), receiver operating curve analysis (ROC) and area under the curve (AUC)/Cstatistic were used. Results: In our cohort of 1,454 patients, the RAI demonstrated superior discriminative ability to the mFI-5 in predicting extended length of stay (C-statistic 0.59, 95% CI 0.56-0.62 vs. C-statistic 0.51, 95% CI: 0.48-0.54, p = 0.0002). The RAI only descriptively appeared superior to mFI-5 in determining mortality (C-statistic 0.89, 95% CI 0.74-0.99 vs. Cstatistic 0.63, 95% CI 0.61-0.66, p=0.11), and NHD (C-statistic 0.68, 95% CI 0.60-0.76 vs. C-statistic 0.60, 95% CI: 0.57-0.62, p=0.15). Conclusions: Pituitary adenomas account for one of the most common brain tumors in the general population, with resection being the preferred treatment for patients with most hormone producing tumors or those causing compressive symptoms. Although pituitary adenoma resection is generally safe, patients who experience post-operative complications frequently share similar pre-operative characteristics and comorbidities. Therefore, appropriate pre-operative risk stratification is imperative for adequate patient counseling and informed consent in these patients. Here we present the first known report showing the superior discriminatory ability of the RAI in predicting eLOS when compared to the mFI-5.

The role of surgical management for prolactin-secreting tumors in the era of dopaminergic agonists: An international multicenter report.

OBJECTIVE: First-line prolactin-secreting tumor (PST) management typically involves treatment with dopamine agonists and the role of surgery remains to be further explored. We examined the international experience of 12 neurosurgical centers to assess the patient characteristics, safety profile, and effectiveness of surgery for PST management. METHODS: Patients surgically treated for PST from January 2017 through December 2020 were evaluated for surgical characteristics, outcomes, and safety. RESULTS: Among 272 patients identified (65.1% female), the mean age was 38.0 ± 14.3 years. Overall, 54.4% of PST were macroadenomas. Minor complications were seen in 39.3% of patients and major complications were in 4.4%. The most common major complications were epistaxis and worsened vision. Most minor complications involved electrolyte/sodium dysregulation. At 3-6 months, local control on imaging was achieved in 94.8% of cases and residual/recurrent tumor was seen in 19.3%. Reoperations were required for 2.9% of cases. On multivariate analysis, previous surgery was significantly predictive of intraoperative complications (6.14 OR, p < 0.01) and major complications (14.12 OR, p < 0.01). Previous pharmacotherapy (0.27 OR, p = 0.02) and cavernous sinus invasion (0.19 OR, p = 0.03) were significantly protective against early endocrinological cure. Knosp classification was highly predictive of residual tumor or PST recurrence on 6-month follow-up imaging (4.60 OR, p < 0.01). There was noted institutional variation in clinical factors and outcomes. CONCLUSION: Our results evaluate a modern, multicenter, global series of PST. These data can serve as a benchmark to compare with DA therapy and other surgical series. Further study and longer term outcomes could provide insight into how patients benefit from surgical treatment.

Clinical Characteristics and Surgical Outcomes of 2542 Patients with Spinal Schwannomas: A Systematic Review and Meta-Analysis.

OBJECTIVE: This study was conducted to systematically analyze the data on the clinical features, surgical treatment, and outcomes of spinal schwannomas. METHODS: We conducted a systematic review and meta-analysis under the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A search of bibliographic databases from January 1, 2001, to May 31, 2021, yielded 4489 studies. Twenty-six articles were included in our final qualitative systematic review and quantitative meta-analysis. RESULTS: Analysis of 2542 adult patients' data from 26 included studies showed that 53.5% were male, and the mean age ranged from 35.8 to 57.1 years. The most common tumor location was the cervical spine (34.2%), followed by the thoracic spine (26.2%) and the lumbar spine (18.5%). Symptom severity was the most common indicator for surgical treatment, with the most common symptoms being segmental back pain, sensory/motor deficits, and urinary dysfunction. Among all patients analyzed, 93.8% were treated with gross total resection, which was associated with better prognosis and less chance of recurrence than subtotal resection. The posterior approach was the most common (87.4% of patients). The average operative time was 4.53 hours (95% confidence interval [CI], 3.18-6.48); the average intraoperative blood loss was 451.88 mL (95% CI, 169.60-1203.95). The pooled follow-up duration was 40.6 months (95% CI, 31.04-53.07). The schwannoma recurrence rate was 5.3%. Complications were particularly low and included cerebrospinal fluid leakage, wound infection, and the sensory-motor deficits. Most of the patients experienced complete recovery or significant improvement of preoperative neurological deficits and pain symptoms. CONCLUSIONS: Our analysis suggests that segmental back pain, sensory/motor deficits, and urinary dysfunction are the most common symptoms of spinal schwannomas. Surgical resection is the treatment of choice with overall good reported outcomes and particularly low complication rates. gross total resection offers the best prognosis with the slightest chance of tumor recurrence and minimal risk of complications.

Half-and-Half Approach for Multiple Aneurysms at the Superior Cerebellar and Middle Cerebral Arteries.

Aneurysms at the superior cerebellar artery (SCA) are commonly treated endovascularly because of their location around the basilar artery,1,2 but they are not intimately related with thalamoperforators. Therefore in younger patients, those with wide-necked aneurysms, or those with multiple ipsilateral aneurysms, surgery remains a treatment option.3 We present a 52-year-old woman with dizziness in whom multiple, unruptured intracranial aneurysms were identified. Imaging demonstrated a 9-mm right-sided SCA aneurysm and 5-mm right and mirror 3-mm left M1 segment middle cerebral artery aneurysms. The patient gave consent to undergo surgery after counseling regarding her treatment options. A pterional and temporal craniotomy was performed to allow for half-and-half subtemporal and transsylvian approaches (Video 1). Here, we discuss the nuances of the approach related to the anatomy of SCA aneurysms. The challenges of the surgery can be mediated with techniques including division of the tentorium for enhanced exposure and early proximal control with temporary clinping or the use of adenosine (cardiac arrest). Our patient remained neurologically stable postoperatively and in 1-year follow-up. SCA aneurysms are easily visualized by the subtemporal and transsylvian approaches; they are frequently located adjacent to the posterior cerebral artery above and the SCA below. A modified transcavernous approach using the orbitozygomatic craniotomy has been described for access to basilar tip aneurysms.4 While comparable, this case demonstrates the efficient workflow to clip multiple aneurysms using a single, combined approach. In patients with multiple aneurysms presenting ipsilaterally or with comorbid conditions that complicate endovascular embolization, surgery should be considered as a definitive and safe treatment strategy. The patient consented to publication.